Surface characterization, in vitro and in vivo biocompatibility of Mg-0.3Sr-0.3Ca for temporary cardiovascular implant.

Magnesium-based alloys are attractive candidate materials for medical applications. Our earlier work showed that the ternary Mg-0.3Sr-0.3Ca alloy exhibits slower degradation rates than both binary Mg-Sr and Mg-Ca alloys. The ternary alloy immersed in simulated body fluid (SBF) forms a compact surface layer of corrosion products that we hypothesized to be a Sr-substituted hydroxyapatite (HA). The main objectives of the current work are to understand the bio-degradation mechanism of Mg-0.3Sr-0.3Ca, to identify the exact nature of its protective layer and to evaluate the in vitro and in vivo biocompatibility of the alloy for cardiovascular applications. To better simulate the physiological environment, the alloy was immersed in SBF which was daily refreshed. Raman spectroscopy and X-Ray photoelectron spectroscopy (XPS) confirmed the formation of a thin, Sr-substituted HA layer at the interface between the alloy and the corrosion products. In vitro biocompatibility evaluated via indirect cytotoxicity assays using HUVECs showed no toxicity effect and ions extracted from Mg-0.3Sr-0.3Ca in fact increased the viability of HUVECs after one week. In vivo tests were performed by implanting a tubular Mg-0.3Sr-0.3Ca stent along with a WE43 control stent into the right and left femoral artery of a dog. Post implantation and histological analyses showed no thrombosis in the artery with Mg-0.3Sr-0.3Ca stent after 5weeks of implantation while the artery implanted with WE43 stent was extensively occluded and thrombosed. Microscopic observation of the Mg-0.3Sr-0.3Ca implant-tissue interface confirmed the in situ formation of Sr-substituted HA on the surface during in vivo test. These results show that the interfacial layer protects the surface of the Mg-0.3Sr-0.3Ca alloy both in vitro and in vivo, and is the key factor in the bio-corrosion resistance of the alloy.

Thermal exposure effects on the in vitro degradation and mechanical properties of Mg-Sr and Mg-Ca-Sr biodegradable implant alloys and the role of the microstructure.

Magnesium is an attractive biodegradable material for medical applications due to its non-toxicity, low density and good mechanical properties. The fast degradation rate of magnesium can be tailored using alloy design. The combined addition of Sr and Ca results in a good combination of mechanical and corrosion properties; the alloy compositions with the best performance are Mg-0.5Sr and Mg-0.3Sr-0.3Ca. In this study, we investigated an important effect, namely thermal treatment (at 400 °C), on alloy properties. The bio-corrosion of the alloys was analyzed via in vitro corrosion tests in simulated body fluid (SBF); the mechanical properties were studied through tensile, compression and three-point bending tests in two alloy conditions, as-cast and heat-treated. We showed that 8h of heat treatment increases the corrosion rate of Mg-0.5Sr very rapidly and decreases its mechanical strength. The same treatment does not significantly change the properties of Mg-0.3Sr-0.3Ca. An in-depth microstructural investigation via transmission electron microscopy, scanning electron microscopy, electron probe micro-analysis and X-ray diffraction elucidated the effects of the thermal exposure. Microstructural characterization revealed that Mg-0.3Sr-0.3Ca has a new intermetallic phase that is stable after 8h of thermal treatment. Longer thermal exposure (24h) leads to the dissolution of this phase and to its gradual transformation to the equilibrium phase Mg17Sr2, as well as to a loss of mechanical and corrosion properties. The ternary alloy shows better thermal stability than the binary alloy, but the manufacturing processes should aim to not exceed exposure to high temperatures (400 °C) for prolonged periods (over 24 h).

Magnesium implant alloy with low levels of strontium and calcium: the third element effect and phase selection improve bio-corrosion resistance and mechanical performance.

Low density, non-toxicity, biodegradability and mechanical properties similar to human tissues such as bone make magnesium (Mg) alloys attractive for biomedical applications ranging from bone to cardiovascular implants. The most important challenge that still prevents the widespread use of Mg implants is their rapid degradation rate. In this study we investigate the combined effect of calcium (Ca) and strontium (Sr) on the corrosion behavior of Mg via in vitro immersion and electrochemical tests in simulated body fluid (SBF), and analyze changes in mechanical properties. We show that the combined addition of 0.3 wt.% Sr and 0.4 wt.% Ca decreases the corrosion rate of Mg both in terms of mass loss and hydrogen evolution more effectively than the single addition of either alloying element. We investigate the microstructure of as-cast specimens and the morphology of the corrosion products using optical microscopy, scanning electron microscopy, electron probe micro-analysis, X-ray diffraction, and X-ray photoelectron spectroscopy. Tensile and three point bending tests reveal that the ternary alloy Mg-0.3Sr-0.3Ca has a good combination of mechanical properties and corrosion resistance with hydrogen evolution rates of 0.01 mL/cm(2)/h in SBF. Higher concentrations of Sr and Ca alter the resulting microstructure leading to increased corrosion rates in SBF by promoting the micro-galvanic corrosion between the α-Mg matrix and intermetallic phases of Mg17Sr2 and Mg2Ca along the grain boundaries. These results indicate that the combined addition of optimal amounts of Ca and Sr is a promising approach to decrease the high degradation rate of Mg implants in physiological conditions, as well as attaining high ductility in the alloy. The better properties of the Mg-0.3Sr-0.3Ca alloy are related to the new intermetallic phases found in this sample. The optimum composition is attributed to the "third element effect", as seen in the corrosion behavior of metallic alloys.

Biocompatibility and biodegradability of Mg-Sr alloys: the formation of Sr-substituted hydroxyapatite.

Magnesium is an attractive material for use in biodegradable implants due to its low density, non-toxicity and mechanical properties similar to those of human tissue such as bone. Its biocompatibility makes it amenable for use in a wide range of applications from bone to cardiovascular implants. Here we investigated the corrosion rate in simulated body fluid (SBF) of a series of Mg-Sr alloys, with Sr in the range of 0.3-2.5%, and found that the Mg-0.5 Sr alloy showed the slowest corrosion rate. The degradation rate from this alloy indicated that the daily Sr intake from a typical stent would be 0.01-0.02 mg day⁻¹, which is well below the maximum daily Sr intake levels of 4 mg day⁻¹. Indirect cytotoxicity assays using human umbilical vascular endothelial cells indicated that Mg-0.5 Sr extraction medium did not cause any toxicity or detrimental effect on the viability of the cells. Finally, a tubular Mg-0.5 Sr stent sample, along with a WE43 control stent, was implanted into the right and left dog femoral artery. No thrombosis effect was observed in the Mg-0.5 Sr stent after 3 weeks of implantation while the WE43 stent thrombosed. X-ray diffraction demonstrated the formation of hydroxyapatite and Mg(OH)2 as a result of the degradation of Mg-0.5 Sr alloy after 3 days in SBF. X-ray photoelectron spectroscopy further showed the possibility of the formation of a hydroxyapatite Sr-substituted layer that presents as a thin layer at the interface between the Mg-0.5 Sr alloy and the corrosion products. We believe that this interfacial layer stabilizes the surface of the Mg-0.5 Sr alloy, and slows down its degradation rate over time.